Lab Notes: New Target for Sepsis Lung Injury

A newly recognized step in development of sepsis-induced lung injury looks like a promising therapeutic target, researchers suggested. Also this week: the need for light in utero.

Stopping Sepsis-Related Lung Injury

Researchers have discovered a potential new therapeutic target for combatting sepsis -- a calcium-signaling pathway.

Bacterial lipopolysaccharides are a major cause of acute lung injury in sepsis. These toxins initially bind to endothelial cell receptors, setting in motion a process that eventually ends in the inflammatory state of sepsis. Not every step in that process is well known, however.

As reported in the Journal of Clinical Investigation, Muniswamy Madesh, PhD, of Temple University in Philadelphia, and colleagues explored the role of a protein called STIM1 (stromal interaction molecule 1), which is involved in calcium signaling.

The researchers found that mice lacking STIM1 in endothelial cells were protected from the lipopolysaccharide-induced lung damage. And using a molecule called BTP2 to block part of the STIM1 signaling pathway in normal mice also prevented toxin-induced damage.

"We've provided evidence indicating that without STIM1 driving calcium signaling, the exacerbation of inflammation can't occur," Madesh said in a statement. "Our results could lead to a whole range of new therapeutic research directions."

-- Todd Neale

Light Key to Healthy Eyes

Developing eyes appear to need light, even in the womb, a mouse study suggested.

A photon or two penetrate into the visceral cavity per cm2 every second in mice, David Copenhagen, PhD, of the University of California San Francisco, and colleagues found.

Mice deprived of that trace of light exposure by being kept in darkness from late gestation through just over a week after birth showed overgrowth of retinal vasculature without normal regression of hyaloid vessels in the eye.

These effects didn't appear dependent on the mother and might play a role in retinopathy of prematurity, in which overactive blood vessel formation in the eye can cause blindness, the group wrote in Nature.

"These data thus show that light -- the stimulus for function of the mature eye -- is also critical in preparing the eye for vision by regulating retinal neuron number and initiating a series of events that ultimately pattern the ocular blood vessels," they concluded.

-- Crystal Phend

Immunotherapy Stalls Breast Cancer Recurrence

A viral vector typically reserved for gene therapy may be able to deliver immunotherapy to prevent breast cancer recurrence, researchers found.

Mice given one of two vaccines that used adeno-associated viruses -- either AAV-5 or AAV-6 -- to deliver a truncated neu oncogene to neu-positive TUBO breast cancers had improved survival at one year, whether they received the immunotherapy orally or via intramuscular injection, according to a study in Molecular Therapy.

The oral dose did appear to work better than the injection, and the AAV-6 serotype offered better outcomes than AAV-5, according to Jason Steel, PhD, of the University of Cincinnati Cancer Institute, and colleagues.

The researchers plan to test the AAV-based oral vaccine in other cancers, including lung cancers.

-- Kristina Fiore

Targeting Depression Through Sleep

The mechanism by which sleep deprivation relieves depression -- albeit transiently -- may have been uncovered by researchers at Tufts University in Boston.

Researchers led by Phillip G. Haydon, PhD, found that astrocytes in the brain regulate the responses to sleep deprivation in mice, through effects on the neuronal adenosine receptor, they reported in Translational Psychiatry.

Efforts to develop therapeutics mimicking the antidepressant effect of sleep deprivation had been hampered by a lack of understanding of the responsible mechanisms.

Haydon and colleagues administered an adenosine receptor agonist to depression-prone mice, and found that 12 hours of sleep deprivation resulted in increased brain levels of adenosine, accompanied by attenuation of the animals' depressive behaviors. In contrast, mice bred to lack adenosine receptors showed no response to sleep deprivation.

The finding suggests that targeting glial receptors could underpin a rapid-onset intervention in acute depression, such as in suicidal patients.

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